Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

We argue that thoughts are structures of concepts, and that concepts should be individuated by their origins, rather than in terms of their semantic or epistemic properties. Many features of cognition turn on the vehicles of content, thoughts, rather than on the nature of the contents they express. Originalism makes concepts available to explain, with no threat of circularity, puzzling cases concerning thought. In this paper, we mention Hesperus/Phosphorus puzzles, the Evans-Perry example of the ship seen through different windows, and (...) Mates cases, and we believe that there are many additional applications. (shrink)

The meaning of the once widely used term the Gibbs Free Energy in terms of available work energy is perfectly illustrated for chemical reactions by the Van’t Hoff Equilibrium Box. Combining this with DeDonder’s extent of reaction variable and using the reaction of $$\hbox {NH}_3$$ to $$\hbox {H}_2$$ and $$\hbox {N}_2$$ at $$200^{\circ }\hbox {C}$$ as an example shows the difference between total work energy and available work energy, and in addition allows calculation of the equilibrium composition, demonstration of the (...) minimum in the Gibbs energy curve, and the standard relationship between $$\Delta _\textrm{r}G^{\circ }$$ and $$\ln {K}$$. (shrink)

[R. M. Sainsbury] Evans argued that most ordinary proper names were Russellian: to suppose that they have no bearer is to suppose that they have no meaning. The first part of this paper addresses Evans's arguments, and finds them wanting. Evans also claimed that the logical form of some negative existential sentences involves 'really' (e.g. 'Hamlet didn't really exist'). One might be tempted by the view, even if one did not accept its Russellian motivation. However, I suggest that Evans gives (...) no adequate account of 'really', and I point to unclarities in Wiggins's similar, but distinct, attempt to use 'really' in the logical form of true negative existentials. /// [David Wiggins] Evans was not wrong (I maintain) to say that the senses of genuine proper names invoke and require objects. Names in fiction or hypothesis mimic such names. Pace Evans, Sainsbury and free logicians, proper names are scopeless. (Evans's 'Julius' is not a name.) Names create a presumption of existential generalization. In sentences such as 'Vulcan does not really exist', that presumption is bracketed. The sentence specifies by reference to story or report a concept identical with Vulcan and declares it be really uninstantiated. (The sentence, which partakes of play, is a kind of palimpsest.) It is explained why this second level view of 'exists' is to be preferred. (shrink)

I had a strange dream, or half-waking vision, not long ago. I found myself at the top of a mountain in the mist, feeling very pleased with myself, not just for having climbed the mountain, but for having achieved my life's ambition, to find a way of answering moral questions rationally. But as I was preening myself on this achievement, the mist began to clear, and I saw that I was surrounded on the mountain top by the graves of all (...) those other philosophers, great and small, who had had the same ambition, and thought they had achieved it. And I have come to see, reflecting on my dream, that, ever since, the hard-working philosophical worms have been nibbling away at their systems and showing that the achievement was an illusion. True, their skeletons, indigestible to worms, remained, and were surprisingly similar to one another. But I was led to think again about what one can, and what one cannot, achieve in this direction. (shrink)

This book is divided into three parts: in Part I, R. M. Hare offers a justification for the use of philosophy of language in the treatment of moral questions, together with an overview of his moral philosophy of ‘universal prescriptivism’. The second part, and the core of the book, consists of five chapters originally presented as a lecture series under the title ‘A Taxonomy of Ethical Theories’. Hare identifies descriptivism and non‐descriptivism as the two main positions in modern moral philosophy. (...) The former he divides into Naturalism and Intuitionism, and the latter into Emotivism and Rationalism. Hare argues that all forms of descriptivism tend to lead to Relativism because the truth conditions of moral statements are culturally variant. Of the positions discussed, only Hare's own position, a form of Rationalism, which he calls Universal Prescriptivism, meets all of the requirements that an adequate ethical theory should meet. Part III consists of Hare's previously published essay ‘Could Kant have been a Utilitarian?’ (Utilitas 5, 1993). Here, Hare puts forward the controversial thesis that Kant's moral philosophy is, in its basic principles, compatible with utilitarianism. (shrink)

Are fictional characters such as Sherlock Holmes real? What can fiction tell us about the nature of truth and reality? In this excellent introduction to the problem of fictionalism R. M. Sainsbury covers the following key topics: what is fiction? realism about fictional objects, including the arguments that fictional objects are real but non-existent; real but non-factual; real but non-concrete the relationship between fictional characters and non-actual worlds fictional entities as abstract artefacts fiction and intentionality and the problem of irrealism (...) fictionalism about possible worlds moral fictionalism. R. M. Sainsbury makes extensive use of examples from fiction, such as Sherlock Holmes, Anna Karenina and Madame Bovary and examines the work of philosophers who have made significant contributions to the topic, including Meinong, David Lewis, and Bas Van Fraassen. Additional features include chapter summaries, annotated further reading and a glossary of technical terms, making _Fiction and Fictionalism_ ideal for those coming to the issue for the first time. (shrink)

Following an introductory classification of prescriptive language that emphasizes the parallel between imperatives and moral language, this chapter distinguishes between the indicative and imperative moods of language. It then dismisses various attempts to account for imperatives, particularly their reduction to indicatives as well as expressivist theories like Ayer's and Stevenson's.

It is my intention in this paper to highlight the dangers which arise when people appeal to moral intuitions to settle questions in political, and in general in applied, philosophy. But first I want to ask why all or nearly all of us are in favour both of liberty and of equality – why all our intuitions are on their side. In the case of liberty it is easy to understand why. Although philosophers have held diverse theories about the concept (...) of liberty – theories which have been drawn together into two main groups in a famous lecture by Sir Isaiah Berlin – there cannot be much doubt that in the mind of the ordinary man to have liberty is to be under no constraint in doing what one wants to do. This, at any rate, is a main constituent of the concept of liberty as all of us understand it. Since, therefore, it seems self-evidently true that we want to be able to do what we want, we are bound to want liberty and, in general, to be in favour of it. We want it for ourselves; if we universalize our prescriptions, this constrains us to be in favour of it for others as well. That explains why, if any politician can claim that he is fighting for liberty, he is likely to win a large following. In the case of equality the matter is not so clear cut. (shrink)

INTERNATIONAL STUDIES IN THE PHILOSOPHY OF SCIENCE Vol. 2, number 1, Autumn 1987, pp. 84-104. R.M. Nugayev. The genesis and structure of models in the modern theory of gravity. Abstract. The analysis of theory-choice problem in modern theory of gravity necessitates consideration of the genesis and the structure of the systems of gravitational abstract objects. My approach to physical theory structure uses and develops the ideas of V.S.Stepin. The basic equations of general relativity - Einstein’s equations – are shown to (...) describe the relations between the abstract objects of the basic model only. The whole theory of gravity chain consists of general relativity, nonmetric theories of gravitation, Newton’s theory of gravitation and special theory of relativity. All these theories describe the relations between the abstract objects of partial ideal models subordinated to the basic one. (shrink)